重组人粒细胞集落刺激因子rhG—CSF的纯化工艺探讨

粒细胞集落刺激因子(granulocyte colony stimulating factor G-CSF)主要来源于巨嗜细胞,内皮细胞及纤维母细胞。能高度特异性的刺激中性白细胞系的功能活化因子。在这里我们对rhG-CSF的纯化工艺进行探讨。通常对rhG-CSF的纯化采用S-200和DE柱进行纯化,在这里我们采用另外一种方法,即采用Q柱和CM柱进行纯化。并对其比较讨论。     

三种干预方法在急性淋巴细胞白血病大剂量甲氨蝶呤化疗性口腔黏膜炎中的应用及临床经济学评价

目的 探讨蜂蜜、低温氧气雾化及常规漱口水对急性淋巴细胞白血病(ALL)患者化疗性口腔黏膜炎(CIOM)的临床效果和成本效益。方法 选取2023年2—5月宁夏银川市某三甲医院血液内科住院治疗且符合纳入排除标准的129例ALL患者,随机分为蜂蜜组、低温氧气雾化组和常规漱口水组,每组43例。化学治疗期间,蜂蜜组用蜂蜜涂抹于口腔黏膜表面;低温氧气雾化组以粒细胞刺激因子为雾化液,经低温氧气雾化吸入;常规漱口水组用医嘱漱口水漱口。结果 蜂蜜组、低温氧气雾化组和常规漱口水组分别有7例(16.28%)、9例(20.93%)和20例(46.51%)患者发生CIOM,三组患者CIOM发生率及严重程度比较,差异具有统计学意义(H=11.598,P=0.003)。蜂蜜与低温氧气雾化对ALL患者CIOM的预防与治疗效果均优于常规漱口水(均P<0.05),但蜂蜜与低温氧气的预防与治疗效果比较,差异无统计学意义(P>0.05)。蜂蜜组的成本低于低温氧气雾化组及常规漱口水组(均P<0.05),低温氧气雾化组虽有一定治疗效果,但成本远高于蜂蜜组与常规漱口水组(均P<0.05)。结论 蜂蜜对ALL...     

预激方案CAG治疗急性髓细胞白血病的疗效及作用机制

目的观察含粒细胞集落刺激因子(G-CSF)的预激方案在治疗初治急性髓细胞白血病(AML)中的疗效,并进一步研究其作用机制。方法13例初治AML患者予以含G-CSF、低剂量阿糖胞苷(Ara-C)和阿克拉霉素(ACR)的CAG方案。以U937细胞株为体外实验模型,流式细胞仪检测细胞早期凋亡标记Annexin V以及进行细胞周期分析。结果一疗程完全缓解率为46.2%(6/13),部分缓解率为38.5%(5/13),总有效率84.7%(11/13);二疗程完全缓解率为76.9%(10/13)。体外实验中,经CAG处理后,早期凋亡标记Annexin V明显升高(P<0.01)。细胞周期检测显示,CAG处理24 h后,S期细胞比例明显升高(P<0.05)。结论G-CSF可增加化疗药物对AML的疗效,其作用机制主要是通过G-CSF促使G0期白血病细胞进入细胞增殖周期,增加细胞周期特异性化疗药物的细胞毒性,诱导细胞凋亡是主要途径。     

Newly discovered innate response activator B cells: crucial responders against microbial sepsis

Evaluation of: Waldmann TA, Conlon KC, Stewart DM et al. Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-β-1 mAb in patients with T-cell large granular lymphocytic leukemia. Blood 121(3), 476–484 (2013).

IL-15 is a cytokine that stimulates the proliferation of NK and T cells. Previous studies have shown that IL-15 is critical to the induction of T-cell large granular lymphocyte (T-LGL) leukemia. A Phase I trial of a humanized antibody (Hu-Mikβ1) to the IL2/IL15Rβ receptor, expressed on T-LGL, is explored in this trial to evaluate the safety, pharmacokinetics, specificity and clinical efficacy of Hu-Mikβ1. The study demonstrated no toxicity and favorable saturation of IL2/IL15Rβ receptor, but no clinical efficacy in this Phase I study.     

Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.     

In vitro and in vivo effects of JAK2 inhibition in chronic myelomonocytic leukemia

In chronic myelomonocytic leukemia (CMML), colony‐forming units granulocyte/macrophage (CFU‐GM), which grow in vitro in the absence of exogenous growth factors, arise from the abnormal clone that is responsible for the overproduction of granulomonocytic cells. Previous in vitro findings including ours suggest that divergent molecular aberrations in CMML seem to converge within the GM‐CSF signaling pathway. As JAK2 is a sentinel kinase in this pathway, JAK2 inhibition may be an attractive treatment approach in CMML. We investigated the in vitro effects of the specific JAK2 inhibitor TG101209 on the autonomous CFU‐GM formation from peripheral blood mononuclear cells of patients with CMML. TG101209 was found to either block or strongly inhibit spontaneous CFU‐GM growth in all 10 patients tested. This inhibitory effect was dose dependent and significantly more pronounced as compared to the inhibitory effect on stimulated CFU‐GM growth from normal individuals. In a CMML patient with splenomegaly, who was treated with the JAK1/2 inhibitor ruxolitinib off label, we can demonstrate a spleen response and the disappearance of constitutional symptoms which was associated with a decrease in autonomous CFU‐GM formation ex vivo. Pharmacological JAK2 inhibition may be an interesting approach to be systematically studied in patients with CMML.     

Pyoderma gangrenosum in an ulcerative colitis patient during treatment with vedolizumab responded favorably to adsorptive granulocyte and monocyte apheresis

Pyoderma gangrenosum (PG) is an extra-intestinal skin lesion in inflammatory bowel disease (IBD) as is erythema nodosum. Vedolizumab (VED) is a monoclonal antibody that targets α4β7 integrin and has an intestinal selective mechanism. Despite good therapeutic effects on colitis, the effect on extra-intestinal manifestations (EIMs) remains unclear. Here we report a case of ulcerative colitis complicated by PG during treatment with VED, which was successfully treated with prednisolone in combination with adsorptive granulocyte and monocyte apheresis (GMA). The patient was a 50-year-old woman with a past medical history of extensive ulcerative colitis managed by golimumab (GLM). She developed flare symptoms due to loss of response to GLM, and treatment was switched to VED. Her gastrointestinal symptoms were improved with VED treatment with less frequent bowel movements. However, infiltrative erythema with pain appeared on the right lower leg and right knee, and expanded and gradually ulcerated. Her skin lesions were treated with corticosteroid, but showed poor improvement. Therefore, granulocyte and monocyte apheresis (GMA) treatment was administered in combination with prednisolone. After 3 months, the ulcer gradually improved, and at the time of this writing, the eruptions were nearly replaced by epithelial tissue. This case study showed that patients with UC and EIMS may respond well to combination therapy of VED and GMA. GMA has a very favorable safety profile. On the other hand, the causal connection between VED and PG is still unclear. We believe that a combination therapy involving VED and GMA in IBD patients with EIMs warrants consideration.     

Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, Inc.     

Ulcerative colitis with hepatitis B virus infection treated successfully by granulocyte monocyte apheresis

Ulcerative colitis (UC) is a major type of idiopathic inflammatory bowel disease (IBD). Immunosuppressive therapies are used to treat IBD patients. Clinicians have strong concerns about using immunosuppressive therapies for IBD patients with hepatitis B virus (HBV) infection because aggressive immunosuppressive therapy can promote reactivation of HBV. For that reason, physicians hesitate to use steroids or other immunosuppressive drugs for IBD patients with HBV infection. Granulocyte monocyte apheresis (GMA) is a safe and effective therapy for UC patients. In Japan, a maximum of 11 sessions of GMA are allowed for moderate‐to‐severe, steroid‐resistant UC patients. However, the effects of GMA on HBV remain unclear. This case report describes a 39‐year‐old man with active UC complicated by HBV infection. Although his symptoms improved with steroid treatment while under entecavir therapy, clinical remission could not be maintained after the steroid dosage was decreased, so GMA was started. After GMA initiation, the frequency of diarrhea decreased and his symptoms improved, and the steroid dosage could be decreased. During the course of GMA, the patient did not experience deterioration in his hepatitis and the HBV DNA level gradually decreased, although GMA itself did not affect the HBV DNA level during each session of GMA. Results show that GMA is a safe and efficacious strategy against UC complicated by HBV without affecting hepatitis because GMA had no remarkable effect on HBV activity. J. Clin. Apheresis 31:584–586, 2016. © 2015 Wiley Periodicals, Inc.     

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Summary. We report a case of aplastic anaemia (AA) treated with granulocyte colony-stimulating factor (G-CSF) terminating as acute myeloblastic leukaemia (AML). Because of severe pneumonia, 250 μg of G-CSF was administered for 30d to promote neutrophil recovery. Following G-CSF therapy, myeoblasts appeared, and the diagnosis of AML was then made. The myeloblasts proliferated in response to G-CSF in vitro and in vivo. In AA. development of AML, after treatment with G-CSF is rate. Therefore a careful observation for leukaemic transformation is necessary in long-term administration of G-CSF for AA.